Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer

Runx1 is a developmentally regulated transcription factor that is essential for haemopoiesis. Runx1 can bind as a monomer to the core consensus sequence TGTGG, but binds more efficiently as a hetero-dimer together with the non-DNA binding protein CBFβ as a complex termed core binding factor (CBF). Here, we demonstrated that CBF can also assemble as a dimeric complex on two overlapping Runx1 sites within the palindromic sequence TGTGGCTGCCCACA in the human granulocyte macrophage colony-stimulating factor enhancer. Furthermore, we demonstrated that binding of Runx1 to the enhancer is rigidly controlled at the level of chromatin accessibility, and is dependent upon prior induction of NFAT and AP-1, which disrupt a positioned nucleosome in this region. We employed in vivo footprinting to demonstrate that, upon activation of the enhancer, both sites are efficiently occupied. In vitro binding assays confirmed that two CBF complexes can bind this site simultaneously, and transfection assays demonstrated that both sites contribute significantly to enhancer function. Computer modelling based on the Runx1/CBFβ/DNA crystal structure further revealed that two molecules of CBF could potentially bind to this class of palindromic sequence as a dimeric complex in a conformation whereby both Runx1 and CBFβ within the two CBF complexes are closely aligned

Marketing digital y el comportamiento del consumidor en la empresa Nefrogolf S.A.C., Lima, 2022

El presente estudio de investigación titulado " Marketing digital y el comportamiento del consumidor en la empresa Nefrogolf S.A.C., Lima, 2022". Cuyo objetivo principal fue analizar la relación entre el marketing digital y el comportamiento del consumidor. El tipo de investigación fue aplicada, enfoque cuantitativo, nivel de estudio correlacional de corte transversal y el diseño no experimental. Se utilizó una muestra censal donde se aplicaron a 50 consumidores de la empresa Nefrogolf. Así mismo se usó como técnica la encuesta y de instrumento el cuestionario con una escala tipo Likert, que permitió medir el coeficiente de fiabilidad del instrumento a través del alfa de Cronbach. Se aplicó la estadística donde se procesaron la información obtenida, donde se mostró que el coeficiente de correlación Rho Spearman = 0.381 Sig. (Bilateral) de 0.006 (<0, <5), concluyendo que existe una relación positiva baja entre el Marketing digital y el comportamiento del consumidor, porque a medida que el marketing digital sea más efectivo, respecto a la promoción de su sitio web, brindando información importante sobre el servicio de diálisis, aumenta la percepción positiva del consumidor y ayuda a la imagen de la empresa, obteniendo reconocimiento importante en los diferentes medios digitales

Factores y variables relevantes que contribuyen a la resiliencia organizacional en restaurantes mype de comida criolla de Lima centro durante la pandemia por Covid-19 entre los años 2020 - 2021: casos múltiples

El presente trabajo pretende identificar los factores y variables relevantes que contribuyen a la Resiliencia Organizacional de los restaurantes MYPE de comida criolla seleccionados en Lima Centro durante la pandemia por el Covid-19 entre los años 2020-2021, a través de un modelo teórico seleccionado. Dicho modelo plantea cuatro factores: Postura Perceptiva, Integridad Contextual, Capacidad Estratégica y Actuación Estratégica. Para la presente investigación se contó con la colaboración de cinco restaurantes MYPES de comida criolla representados por sus dueños o gerentes, quienes brindaron información relevante para el trabajo de campo. Esta información fue respaldada por trabajadores de los restaurantes seleccionados, expertos en el sector y un trabajo de observación por parte de los investigadores. Como resultado de esta investigación de enfoque cualitativo, se obtuvo que tres factores fueron relevantes por contribuir a la Resiliencia Organizacional de los restaurantes sujetos de estudio: Postura Perceptiva, Capacidad Estratégica y Actuación Estratégica. Estos se identificaron por medio de sus variables respectivament

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance

BACKGROUND: There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance. RESULTS: We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset – potentially more contaminant - are taken into account. Data on hospital discharges and surgical procedures were obtained from Danish and Swedish national in-patient hospital registries for 167 sCJD cases, onset 1987–2003, and for 835 matched and 2,224 unmatched population controls. Surgery was allocated to different life-time periods as previously reported, and frequencies were compared using logistic regression analysis. In the year preceding clinical onset, persons with sCJD underwent a statistically significant higher number of minor surgical interventions (OR (95% CI): 17.50 (3.64-84.24)), transluminal endoscopies (OR: 2.73 (1.01–7.37)) and gastrointestinal operations (OR: 3.51 (1.21–10.19)) compared to matched controls. Surgical discharges clustered towards clinical onset. These differences increased during the clinical period, with statistically significant higher frequencies for both endoscopies and minor surgery (OR: 13.91 (5.87-32.95), and for main surgical procedures (OR: 2.10 (1.00-4.39)), particularly gastrointestinal surgery (OR: 6.00 (1.83-19.66)), and surgery contacting skeletal muscle. Comparisons with unmatched controls yielded similar results for neurosurgery in the clinical period (OR: 19.40 (2.22-168.34)). CONCLUSIONS: These results suggest that some types of surgical procedures are associated with sCJD, after clinical onset or particularly just before onset. Selective planning of such surgery to minimize instrument/device contamination or quarantining might be feasible. Conditional to progress in sCJD etiological research, results are relevant for guidance development

Towards an age-dependent transmission model of acquired and sporadic Creutzfeldt-Jakob disease

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood. METHODS: From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge. RESULTS: The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56-64.0) in patients <30 years, 3.04 (95% 1.26-7.33) in 30-39 years, and 1.75 (95% CI 0.89-3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures. CONCLUSIONS: Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery.Funding was obtained from the EU Research Commission, Concerted Action QLRG3-CT-2002-81223 NEUROPRION and the Spanish Centro de Investigaciones en enfermedades Neurológicas (CIEN C03-06), and Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED) networks, and from the Karolinska and Carlos III National Health Institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Peer audience effects on children’s vocal masculinity and femininity

Existing evidence suggests that children from around the age of 8 years strategically alter their public image in accordance with known values and preferences of peers, through the self-descriptive information they convey. However, an important but neglected aspect of this ‘self-presentation’ is the medium through which such information is communicated: the voice itself. The present study explored peer audience effects on children's vocal productions. Fifty-six children (26 females, aged 8–10 years) were presented with vignettes where a fictional child, matched to the participant's age and sex, is trying to make friends with a group of same-sex peers with stereotypically masculine or feminine interests (rugby and ballet, respectively). Participants were asked to impersonate the child in that situation and, as the child, to read out loud masculine, feminine and gender-neutral self-descriptive statements to these hypothetical audiences. They also had to decide which of those self-descriptive statements would be most helpful for making friends. In line with previous research, boys and girls preferentially selected masculine or feminine self-descriptive statements depending on the audience interests. Crucially, acoustic analyses of fundamental frequency and formant frequency spacing revealed that children also spontaneously altered their vocal productions: they feminized their voices when speaking to members of the ballet club, while they masculinized their voices when speaking to members of the rugby club. Both sexes also feminized their voices when uttering feminine sentences, compared to when uttering masculine and gender-neutral sentences. Implications for the hitherto neglected role of acoustic qualities of children's vocal behaviour in peer interactions are discussed

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. Background: CMR is the reference tool for cardiac imaging but is time-consuming. Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine&#43;LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in less than 1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort. (J Am Coll Cardiol Img 2021;14:1742–1754)Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia : the ANGIOCOR prospective cohort study protocol

Background: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. Methods: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. Discussion: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. Trial registration: NCT04162236